The overarching goal of this renewal application is to continue the progress achieved in the current grant support period, extending the adaptive treatment strategy approach to several new areas of mental health treatment research. We conceptualize adaptive treatment strategies as dynamic algorithms for matching clinical decisions to the evolving course of a patient's response to treatment over time. To date, we have provided a general template for randomized clinical trials designed to discover the optimal symptom-based threshold for deciding to switch from a front-line treatment to a second-line treatment. In the current application, we propose to develop designs for three critical areas of adaptive treatments, in response to NIMH-sponsored strategic planning efforts that give high priority to the development of clinical trials that can help guide treatment decisions faced by clinicians treating real patients. Our main aims are: 1. Develop placebo-free non- equivalence designs for pre-marketing studies. These adaptive treatment designs could provide evidence for efficacy of a new treatment for a wide range of disorders, while avoiding or minimizing the use of placebo controls. This Aim responds to the call for new methodologies for treatment research that addresses the ethical dilemmas posed by placebo control. 2. Develop a prototype design for the treatment of children with bipolar illness. This adaptive treatment design will address the issue of whether to switch or augment medication in young patients with mania, a group often characterized by heterogenous response to treatment. This Aim will parallel the work of the Treatment of Early Age Mania study group. This Aim should help make possible clinical trials in children that are more attractive and feasible, through the use of adaptive study treatments that better fit the needs of pediatric populations. 3. Develop a prototype design for prevention of first psychotic break in high- risk individuals. This adaptive treatment design will identify the optimal threshold for beginning anti-psychotic treatment, as well as address the crucial issue of discontinuation of anti- psychotic medication in patients who remain unaffected. This Aim will parallel the planning effort of the International Study for Early Detection and Intervention in the Schizophrenia Prodrome study. This Aim extends the current methods for adaptive treatment trials to the "two-threshold" context of starting and stopping treatment that typifies clinical decision-making in mental health.